Formulation of a riluzole solution with beta-cyclodextrins

Abstract

The present invention provides methods for parenterally administering riluzole to subjects in need of treatment.

What is claimed is: 
     
       1. A method for treating a subject in need thereof, the method comprising parenterally administering to the subject riluzole at a dose that is less than 10 mg per day and further administering riluzole orally at 50 mg twice a day. 
     
     
       2. The method of  claim 1 , wherein the parenterally administered daily dose is about 0.4 mg to about 9.5 mg or about 0.4 mg to about 7.5 mg. 
     
     
       3. The method of  claim 1 , wherein the parenterally administered daily dose is about 0.4 mg to about 5 mg. 
     
     
       4. The method of  claim 1 , wherein the parenterally administered daily dose is about 0.4 mg to about 4 mg. 
     
     
       5. The method of  claim 1 , wherein the parenterally administered daily dose is about 0.1 mg to about 4 mg. 
     
     
       6. The method of  claim 1 , wherein the parenterally administered daily dose is about 1 mg to about 4 mg. 
     
     
       7. The method of  claim 1 , wherein the parenterally administered riluzole is injected or infused into the subject's brain, spinal cord, or a cerebral ventricle. 
     
     
       8. The method of  claim 1 , wherein the parenterally administered riluzole is intrathecally administered and, optionally, wherein administration occurs continuously. 
     
     
       9. The method of  claim 7 , wherein parenteral administration does not result in a substantial increase in serum AUC of riluzole or a metabolite thereof. 
     
     
       10. The method of  claim 1 , wherein the parenterally administered riluzole is formulated as a composition comprising about 0.4 mg to about 10 mg per ml of riluzole dissolved in at least 1% (w/v) ß-cyclodextrin and an aqueous solvent, and wherein the composition a pH of about 5 to about 8. 
     
     
       11. The method of  claim 10 , wherein the parenterally administered riluzole composition comprises about 0.4 mg to about 10 mg per ml of riluzole dissolved in about 1% (w/v) to about 15% (w/v) ß-cyclodextrin and an aqueous solvent. 
     
     
       12. The method of  claim 10 , wherein the parenterally administered riluzole composition comprises about 0.4 mg to about 10 mg per ml of riluzole dissolved in about 1% (w/v) to about 10% (w/v) ß-cyclodextrin and an aqueous solvent. 
     
     
       13. The method of  claim 10 , wherein the parenterally administered riluzole composition comprises about 0.4 mg to about 4 mg per ml of riluzole dissolved in about 1% (w/v) to about 5% (w/v) ß-cyclodextrin and an aqueous solvent. 
     
     
       14. The method of any one of  claim 10 , wherein the parenterally administered riluzole composition further comprises one or more pharmaceutically acceptable excipient and/or one or more additional active ingredient. 
     
     
       15. The method of  claim 10 , wherein the ß-cyclodextrin is selected from the group consisting of 2,6-di-O-methyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, and sulfobutylether β-cyclodextrin. 
     
     
       16. The method of  claim 10 , wherein the aqueous solvent is water, saline, or dextrose. 
     
     
       17. The method of  claim 1 , wherein treatment alleviates one or more symptoms in the subject, delays progression of a disease in the subject, slows progression of a disease in the subject, or extends survival of the subject. 
     
     
       18. The method of  claim 1 , wherein the subject in need of treatment with riluzole is a subject with motor neuron disease, spinal muscular atrophy, spinal cord injury, Parkinson's disease, Multiple Sclerosis, Alzheimer's disease, depression, Tourette Syndrome, general anxiety disorders, schizophrenia, or bipolar disorder. 
     
     
       19. The method of  claim 18 , wherein the subject in need of treatment with riluzole is a subject with amyotrophic lateral sclerosis.